Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Dec 25;4(1):1-17.
doi: 10.3390/jcm4010001.

Clinical Results of Hypomethylating Agents in AML Treatment

Marjan Cruijsen  1 , Michael Lübbert  2 , Pierre Wijermans  3 , Gerwin Huls  4
Affiliations
Review

Clinical Results of Hypomethylating Agents in AML Treatment

Marjan Cruijsen et al. J Clin Med. .

Abstract

Epigenetic changes play an important role in the development of acute myeloid leukemia (AML). Unlike gene mutations, epigenetic changes are potentially reversible, which makes them attractive for therapeutic intervention. Agents that affect epigenetics are the DNA methyltransferase inhibitors, azacitidine and decitabine. Because of their relatively mild side effects, azacitidine and decitabine are particularly feasible for the treatment of older patients and patients with co-morbidities. Both drugs have remarkable activity against AML blasts with unfavorable cytogenetic characteristics. Recent phase 3 trials have shown the superiority of azacitidine and decitabine compared with conventional care for older AML patients (not eligible for intensive treatment). Results of treatment with modifications of the standard azacitidine (seven days 75 mg/m(2) SC; every four weeks) and decitabine (five days 20 mg/m(2) IV; every four weeks) schedules have been reported. Particularly, the results of the 10-day decitabine schedule are promising, revealing complete remission (CR) rates around 45% (CR + CRi (i.e., CR with incomplete blood count recovery) around 64%) almost comparable with intensive chemotherapy. Application of hypomethylating agents to control AML at the cost of minimal toxicity is a very promising strategy to "bridge" older patients with co-morbidities to the potential curative treatment of allogeneic hematopoietic cell transplantation. In this article, we discuss the role of DNA methyltransferase inhibitors in AML.

Keywords: AML; azacitidine; decitabine; elderly; epigenetics; hypomethylating agents.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Mechanism of action of hypomethylating agents. (Black circles, methylated CpG; white circles, unmethylated CpG.)
See this image and copyright information in PMC

References

    1. Gronbaek K., Hother C., Jones P.A. Epigenetic changes in cancer. APMIS. 2007;115:1039–1059. doi: 10.1111/j.1600-0463.2007.apm_636.xml.x. - DOI - PubMed
    1. Jones P., Baylin S.B. The epigenomics of cancer. Cell. 2007;128:683–692. doi: 10.1016/j.cell.2007.01.029. - DOI - PMC - PubMed
    1. Figueroa M.E., Skrabanek L., Li Y., Jiemjit A., Fandy T.E., Paietta E., Fernandez H., Tallman M.S., Greally J.M., Carraway H., et al. MDS and secondary AML display unique patterns and abundance of aberrant DNA methylation. Blood. 2009;114:3448–3458. doi: 10.1182/blood-2009-01-200519. - DOI - PMC - PubMed
    1. Figueroa M.E., Lugthart S., Li Y., Erpelinck-Verschueren C., Deng X., Christos P.J., Schifano E., Booth J., van Putten W., Skrabanek L., et al. DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia. Cancer Cell. 2010;17:13–17. doi: 10.1016/j.ccr.2009.11.020. - DOI - PMC - PubMed
    1. Cancer Genome Atlas Research Network Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl. J. Med. 2013;368:2059–2074. - PMC - PubMed

LinkOut - more resources